Eaf1 and Eaf2 negatively regulate canonical Wnt/beta-catenin signaling
文献类型：期刊论文
| 作者 | Liu, Jing-Xia1; Zhang, Dawei1; Xie, Xunwei1; Ouyang, Gang1; Liu, Xing1; Sun, Yonghua2; Xiao, Wuhan1 |
| 刊名 | DEVELOPMENT
 |
| 出版日期 | 2013-03-01 |
| 卷号 | 140期号:5页码:1067-1078 |
| 关键词 | Eaf1 Eaf2 Wnt beta-catenin Tumor suppressor |
| ISSN号 | 0950-1991 |
| 通讯作者 | Xiao, WH (reprint author), Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan 430072, Peoples R China. |
| 中文摘要 | Eaf factors play a crucial role in tumor suppression and embryogenesis. To investigate the potential mechanism of Eaf activity, we performed loss-and gain-of-function assays in zebrafish using morpholino and mRNA injections, respectively. We found that eaf1 and eaf2 inhibit Wnt/beta-catenin signaling, thereby modulating mesodermal and neural patterning in the embryo. Moreover, ectopic expression of eaf1 and eaf2 in embryos and cultured cells blocked beta-catenin reporter activity. By immunoprecipitation, we also observed that Eaf1 and Eaf2 bound to the Armadillo repeat region and C-terminus of beta-catenin, as well as to other beta-catenin transcription complex proteins, such as c-Jun, Tcf and Axin, suggesting the formation of a novel complex. In addition, the N-terminus of Eaf1 and Eaf2 bound to beta-catenin and exhibited dominant-negative activity, whereas the C-terminus appeared to either harbor a suppression domain or to recruit a repressor. Both the N- and C-terminus must be intact for Eaf1 and Eaf2 suppressive activity. Lastly, we demonstrate a conservation of biological activities for Eaf family proteins across species. In summary, our evidence points to a novel role for Eaf1 and Eaf2 in inhibiting canonical Wnt/beta-catenin signaling, which might form the mechanistic basis for Eaf1 and Eaf2 tumor suppressor activity. |
| 英文摘要 | Eaf factors play a crucial role in tumor suppression and embryogenesis. To investigate the potential mechanism of Eaf activity, we performed loss-and gain-of-function assays in zebrafish using morpholino and mRNA injections, respectively. We found that eaf1 and eaf2 inhibit Wnt/beta-catenin signaling, thereby modulating mesodermal and neural patterning in the embryo. Moreover, ectopic expression of eaf1 and eaf2 in embryos and cultured cells blocked beta-catenin reporter activity. By immunoprecipitation, we also observed that Eaf1 and Eaf2 bound to the Armadillo repeat region and C-terminus of beta-catenin, as well as to other beta-catenin transcription complex proteins, such as c-Jun, Tcf and Axin, suggesting the formation of a novel complex. In addition, the N-terminus of Eaf1 and Eaf2 bound to beta-catenin and exhibited dominant-negative activity, whereas the C-terminus appeared to either harbor a suppression domain or to recruit a repressor. Both the N- and C-terminus must be intact for Eaf1 and Eaf2 suppressive activity. Lastly, we demonstrate a conservation of biological activities for Eaf family proteins across species. In summary, our evidence points to a novel role for Eaf1 and Eaf2 in inhibiting canonical Wnt/beta-catenin signaling, which might form the mechanistic basis for Eaf1 and Eaf2 tumor suppressor activity. |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| 类目[WOS] | Developmental Biology |
| 研究领域[WOS] | Developmental Biology |
| 关键词[WOS] | ELONGATION-FACTOR ELL ; BETA-CATENIN ; ANTERIOR NEUROECTODERM ; EMBRYONIC AXIS ; HEAD INDUCTION ; ZEBRAFISH WNT8 ; C-MYC ; PROTEINS ; PATHWAY ; MOUSE |
| 收录类别 | SCI |
| 资助信息 | National Natural Science Foundation of China (NSFC) [91019008, 30971667, 31071212, 20890113]; National Transgene Project [2009ZX08010-021B]; Chinese Academy of Science [KSCX2-EW-Q-12] |
| 语种 | 英语 |
| WOS记录号 | WOS:000314879800015 |
| 公开日期 | 2013-10-31 |
| 源URL | [http://ir.ihb.ac.cn/handle/342005/19341]  |
| 专题 | 水生生物研究所_水生生物分子与细胞生物学研究中心_期刊论文 |
| 作者单位 | 1.Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan 430072, Peoples R China 2.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Jing-Xia,Zhang, Dawei,Xie, Xunwei,et al. Eaf1 and Eaf2 negatively regulate canonical Wnt/beta-catenin signaling[J]. DEVELOPMENT,2013,140(5):1067-1078. |
| APA | Liu, Jing-Xia.,Zhang, Dawei.,Xie, Xunwei.,Ouyang, Gang.,Liu, Xing.,...&Xiao, Wuhan.(2013).Eaf1 and Eaf2 negatively regulate canonical Wnt/beta-catenin signaling.DEVELOPMENT,140(5),1067-1078. |
| MLA | Liu, Jing-Xia,et al."Eaf1 and Eaf2 negatively regulate canonical Wnt/beta-catenin signaling".DEVELOPMENT 140.5(2013):1067-1078. |
入库方式： OAI收割
来源：水生生物研究所
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